We have continued to examine the relationships between cortical and subcortical systems, particularly between catecholamines in the prefrontal cortex (PFC) and the nucleus accumbens and corpus striatum. Using sensitive measures of activity we have determined that following chemical lesioning of efferents from the prefrontal cortex rats develop a state both of basal hyperactivity and hyperexploration. As recovery occurs, firs the hyperactivity and then the increased exploratory behavior decline to near baseline levels by one month after the lesion. Neurochemical changes occur in parallel with those in activity. Following chemical destruction of PFC efferents, dopamine turnover in the PFC, the cingulate cortex and in the striatum are increased. These changes disappear by one month after the lesion. It appears that the prefrontal cortex can modulate catecholamine turnover and some associated behaviors both in other cortical and in subcortical areas.